Vasculogenesis or angiogenesis is the formation of new vessels, and is important in the embryo stage and also in adults. In the embryo stage, mesoderm-derived endothelial precursors (angioblasts) differentiate into endothelial cells, thereby forming a vessel. Angiogenesis also occurs in adults, and generally an angiogenic cytokine, particularly, a growth factor such as vascular endothelial growth factor (VEGF), directly acts on a reporter of vascular endothelial cells to promote angiogenesis. Particularly, VEGF-A of the VEGF family stimulates VEGFR2, which is a receptor thereof in a vascular endothelial cell, to provoke angiogenesis. Such an angiogenesis-stimulating cytokine may be secreted by blood cells or stromal cells.
Therefore, research has been conducted for developing an agent for treating a disease caused by angiogenesis by neutralizing a vessel-promoting factor or inhibiting a receptor thereof, and as a critical material for treating a disease caused by angiogenesis, an anti-VEGF agent has been used. For example, treatment agents targeting VEGF-A are critical in their use in cancers or retinal diseases, and particularly, Bevacizumab (trade name: Avastin) is an antibody of VEGF-A that has been proven to prevent recurrence and to extend of life in colon cancer and thus is expected to be effective on other types of cancer. However, an anti-VEGF agent reduces integrity of vessels and causes bleeding, and has side effects such as an increasing blood pressure (Elice F et al., Thrombosis Research (2012)).
For this reason, a substance capable of minimizing such side effects and inhibiting functions of various angiogenesis-stimulating factors while inhibiting VEGF has become a major subject for research, however the research that has been carried out and has still not produced sufficient results.